Open AccessTransducer of erbB2.1 is a potential cellular target of gefitinib in lung cancer therapy
Author(s) -
Kekang Sun,
Yang Yang,
Lin Zhao,
Lili Wang,
Yang Jiao
Publication year - 2012
Publication title -
oncology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.766
H-Index - 54
eISSN - 1792-1082
pISSN - 1792-1074
DOI - 10.3892/ol.2012.969
Subject(s) - gefitinib , cell cycle , cyclin d1 , cancer research , epidermal growth factor receptor , cell cycle checkpoint , lung cancer , oncogene , cell growth , gene knockdown , medicine , cancer , biology , oncology , cell culture , genetics
Gefitinib, the specific inhibitor of the epidermal growth factor receptor (EGFR), may cause growth delay in cancer cell lines. Thorough understanding of the downstream cellular signaling of gefitinib will facilitate the discovery of biomarkers for predicting outcomes and monitoring anti-EGFR therapies, and provide information for key targets for therapeutic intervention. In this study, we investigated the role of transducer of erbB2.1 (TOB1) in gefitinib therapy. Using the lung carcinoma cell lines A549 and NCI-H1975, the results suggested that gefitinib might mediate cell cycle arrest in lung cancer cells at least by targeting TOB1 expression. Gefitinib treatment caused cell cycle arrest predominantly at the G1 phase, which is associated with TOB1 nuclear translocation and its interaction with cyclin D1. We also showed that knockdown of TOB1 expression by RNAi rescued lung cancer cells from gefitinib-induced cell-proliferative arrest. These results suggest that TOB1 interaction with cyclin D1 and nuclear translocation is directly involved in the gefitinib-induced anti-proliferative cell cycle arrest.